Chest Tube Blood Loss Research Articles

Role of Omega-6 Fatty Acid Metabolism in Cardiac Surgery Postoperative Bleeding Risk.

OBJECTIVES:Cardiac surgery is frequently associated with significant postoperative bleeding. Platelet-dysfunction is the main cardiopulmonary bypass (CPB)-induced hemostatic defect. Not only the number of platelets decreases, but also the remaining are functionally impaired. Although lipid metabolism is crucial for platelet function, little is known regarding platelet metabolic changes associated with CPB-dysfunction. Our aim is to explore possible contribution of metabolic perturbations for platelet dysfunction after cardiac surgery.DESIGN:Prospective cohort study.SETTING:Tertiary academic cardiothoracic-surgery ICU.PATIENTS:Thirty-three patients submitted to elective surgical aortic valve replacement.INTERVENTIONS:Samples from patients were collected at three time points (preoperative, 6- and 24-hr postoperative). Untargeted metabolic analysis using high-performance liquid chromatography-tandem mass spectrometry was performed to compare patients with significant postoperative bleeding with patients without hemorrhage. Principal component analyses, Wilcoxon matched-pairs signed-rank tests, adjusted to FDR, and pairwise comparison were used to identify pathways of interest. Enrichment and pathway metabolomic complemented the analyses.MEASUREMENTS AND MAIN RESULTS:We identified a platelet-related signature based on an overrepresentation of changes in known fatty acid metabolism pathways involved in platelet function. We observed that arachidonic acid (AA) levels and other metabolites from the pathway were reduced at 6 and 24 hours, independently from antiagreggation therapy and platelet count. Concentrations of preoperative AA were inversely correlated with postoperative chest tube blood loss but were not correlated with platelet count in the preoperative, at 6 or at 24 hours. Patients with significant postoperative blood-loss had considerably lower values of AA and higher transfusion rates. Values of postoperative interleukin-6 were strongly correlated with AA variability.CONCLUSIONS AND RELEVANCE:Our observations suggest that an inflammatory-related perturbation of AA metabolism is a signature of cardiac surgery with CPB and that preoperative levels of AA may be more relevant than platelet count to anticipate and prevent postoperative blood loss in patients submitted to cardiac surgery with CPB.

Predictive Factors and Outcomes for Successful Thoracoscopic Lung Resection in Pediatric Patients

Less than 50% of children with congenital lung lesions are treated thoracoscopically. There are variable data regarding the benefits and limited information on factors contributing to successful thoracoscopic lobectomies in pediatric patients. We sought to identify predictive factors leading to safe and efficient thoracoscopic lung resection. We performed a single-center, retrospective chart review of patients (age <18 y) who underwent lung resection between June 2009 and July 2020. Pulmonary wedge resection was excluded. Data collected included demographics, perioperative findings, such as symptoms or infection, and postoperative outcomes. Univariate, multivariate, and sensitivity analyses were performed. Ninety-six patients were identified. Sixty-nine patients (72%) underwent initial thoracoscopy, with 15 (22%) converting to open thoracotomy (CTO). Forty-one (43%) patients had preoperative symptoms and 15 (15.6%) had an active infection. Among symptomatic patients, 18 (43.9%) underwent thoracotomy and 23 (56%) were attempted thoracoscopically, 13 (31%) of whom were completed thoracoscopically. On univariate analysis, age >1 year, infection, preoperative symptoms, and intraoperative adhesions were associated with CTO. Older age (odds ratio [OR]= 1.041) and estimated blood loss (EBL) (OR= 2.398) were significant prognostic factors of CTO on logistic regression. Thoracoscopy was significantly associated with decreased length of stay, opioid use, chest tube duration, blood loss and need for blood transfusion. There was no difference in operative time, 30-day readmission, or mortality. Thoracoscopy has become a standard approach for pediatric lung resection. Our findings indicate that age < 1 year and the absence of active respiratory infection and preoperative symptoms may be predictive of successful completion of the thoracoscopic approach. Thoracoscopy offers significant advantages over the traditional open thoracotomy with regard to blood loss and opioid requirements, LOS, and chest tube duration.

Blood Loss Kinetics During the First 12 Hours After On-Pump Cardiac Surgical Procedures

Anemia and coagulation management and a restrictive transfusion strategy are key points of blood management in patients undergoing cardiac surgical procedures. However, little consideration has been given to the kinetics of postoperative bleeding. This prospective observational study investigated bleeding kinetics from chest tubes to assess whether it was possible to predict, within the early postoperative hours, major bleeding at 12 postoperative hours. Adult cardiac surgical patients who were admitted consecutively to the postoperative intensive care unit in a tertiary academic hospital from January to June 2016 were included. Blood volume was collected from the chest drains, and major bleeding was defined as bleeding exceeding the 90th percentile of the volume distribution at 12 postoperative hours. Receiver operating characteristics curve analysis was performed with hourly bleeding thresholds to determine the best predictor of major bleeding. In 292 patients, bleeding at 12 postoperative hours ranged from 60 to 2190 mL (median, 350 mL), and 30 patients had major bleeding, with a threshold of 675 mL. Bleeding volume declined logarithmically, 54% [IQR, 45% to 63%] within the first 4 hours. Patients with major bleeding had a higher bleeding volume every hour (P < .004). A good predictive value was observed within the first 2 hours (2.73 mL/kg; receiver operating characteristics area under the curve, 0.87 ± 0.04 [IQR, 0.79 to 0.94]; P< .001). The hourly rate of chest tube blood loss seems to be relevant to predict, within the first postoperative hours after cardiac surgical procedures, major bleeding at 12 postoperative hours. Early detection of blood loss may help to improve a patient's blood conservation strategy because it may prompt preemptive treatments.

Will high-dose heparin affect blood loss and inflammatory response in patients undergoing cardiopulmonary bypass?

We performed a randomized study to investigate if a high versus a standard dose of heparin dose during cardiopulmonary bypass could affect intra- and post-operative bleeding and reduce the inflammatory response. A total of 30 patients undergoing elective coronary artery bypass grafting were randomized into high or standard dose of heparin during cardiopulmonary bypass. Blood loss was documented peri- and post-operatively, and interleukin-6, tumor necrosis factor-α, and C3 were measured in conjunction with cardiopulmonary bypass. Data from 29 patients were analyzed after exclusion of one patient. The mean initial bolus and total heparin doses were 43,000 ± 5,800 IU versus 35,000 ± 4,100 IU, (p < 0.001), and 58,000 ± 9,500 IU versus 45,000 ± 7,900 IU, (p < 0.001) in the intervention and the control group, respectively. The median intra-operative bleeding was 150 mL (interquartile range 100-325) in the control versus 225 mL (IQR 200-350) in the intervention group, p = 0.15. The median chest tube blood loss 12 hour post-operatively was 300 mL (interquartile range 250-385) in the control versus 450 mL (IQR 315-505) in the intervention group, p = 0.029. There was no significant difference between the control group and the intervention group during cardiopulmonary bypass for the measured inflammatory markers interleukin-6 (p = 0.98), tumor necrosis factor-α (p = 0.72), or C3 (p = 0.13). This small study showed a small increase of post-operative bleeding associated with higher heparin dosage in conjunction with cardiopulmonary bypass but did not demonstrate an effect of heparin on the inflammatory response to cardiopulmonary bypass.

Targeted Bleeding Management Reduces the Requirements for Blood Component Therapy in Lung Transplant Recipients

Objective Lung transplantation is associated with high rates of bleeding and frequent blood transfusion. The authors aimed to determine if point-of-care coagulation testing (POCCT) reduced transfusion requirements. Design, Settings, and Participants A before-and-after cohort analysis conducted at a single tertiary referral center. Ninety-three sequential adult patients between January 2010 and January 2014 undergoing isolated lung transplant without preoperative extracorporeal support were analyzed. Intervention ROTEM and multi-plate POCCT were introduced on July 1, 2012, with an associated algorithm based on the results. Measurements and Main Results Statistically significant decreases in the proportion of patients receiving PRBCs (87% v 65%; p = 0.015), FFP (72% v 30%; p v 37%; p = 0.002) were found after the intervention. There were small decreases in median chest tube blood loss at 2 hours (300 mLs v 215 mLs; p = 0.03) and 4 hours (440 mLs v 350 mLs; p = 0.050) but not at 12 hours postoperatively. There were no changes in reoperation for bleeding (9% v 4%; p = 0.158) or in-hospital mortality (6% v 2%; p = 0.617). The cost of blood products administered decreased from a median of $3,935.00 to $991.00 (p Conclusions Use of POCCT in lung-transplant surgery is associated with significant reductions in blood product use and cost. There were no detectable changes in outcome aside from a small decrease in early postoperative bleeding.

Development and implementation of a clinical pathway for cardiac surgery in the intensive care unit: Effects on protocol adherence.

Cardiac surgery (CS) is facilitated by multiple perioperative guidelines and protocols. Use of a clinical pathway (CP) may facilitate the care of these patients. This is a pre-post design study in the ICU of a tertiary referral centre. A CP for CS patients in the ICU was developed by ICU-nurses and enabled them to execute proactively predefined actions in accordance with and within the preset boundaries which were part of a variance report. A tailored implementation strategy was used. Primary outcome measure was protocol adherence above 80% on the domains of blood pressure control, action on chest tube blood loss and electrolyte control within the CP. In a 4-month period, 84 consecutive CP patients were included and compared with 162 matched control patients admitted in the year before implementation; 3 patients were excluded. Propensity score was used as matching parameter. CP patients were more likely to receive early adequate treatment for derangements in electrolytes (96% vs 47%, P<.001), blood pressure (90% vs 49%, P<.001) and adequate treatment for chest tube blood loss (90% vs 10%, P<.001). We found no differences in hospital and ICU LOS, ICU readmission or mortality. Use of the CP improved postoperative ICU treatment for cardiac surgical patients. Implementation of a CP and the use of a special variance report could be a blueprint for the implementation and use of a CP in low-volume high complex surgery.

Targeted Bleeding Management Reduces the Requirements for Blood Component Therapy in Lung Transplant Recipients

Lung transplantation is associated with high rates of bleeding and frequent blood transfusion. The authors aimed to determine if point-of-care coagulation testing (POCCT) reduced transfusion requirements. A before-and-after cohort analysis conducted at a single tertiary referral center. Ninety-three sequential adult patients between January 2010 and January 2014 undergoing isolated lung transplant without preoperative extracorporeal support were analyzed. ROTEM and multi-plate POCCT were introduced on July 1, 2012, with an associated algorithm based on the results. Statistically significant decreases in the proportion of patients receiving PRBCs (87% v 65%; p = 0.015), FFP (72% v 30%; p<0.0001) and platelets (70% v 37%; p = 0.002) were found after the intervention. There were small decreases in median chest tube blood loss at 2 hours (300 mLs v 215 mLs; p = 0.03) and 4 hours (440 mLs v 350 mLs; p = 0.050) but not at 12 hours postoperatively. There were no changes in reoperation for bleeding (9% v 4%; p = 0.158) or in-hospital mortality (6% v 2%; p = 0.617). The cost of blood products administered decreased from a median of $3,935.00 to $991.00 (p<0.001). Use of POCCT in lung-transplant surgery is associated with significant reductions in blood product use and cost. There were no detectable changes in outcome aside from a small decrease in early postoperative bleeding.

The effect of normovolemic modified ultrafiltration on inflammatory mediators, endotoxins, terminal complement complexes and clinical outcome in high-risk cardiac surgery patients

The clinical benefit of normovolemic modified ultrafiltration (N-MUF) after cardiac surgery is still debated. As we have shown in a previous publication, there is a significant improvement in platelet function, so we were interested in whether ultrafiltration can reduce plasma levels of endotoxins, terminal complement complexes and cytokines after cardiopulmonary bypass (CPB) in adults with increased risk profiles. In this single-center, prospective, randomized trial, fifty high-risk patients (mean logistic EuroSCORE II: 17.5%) who underwent cardiac surgery were randomized. After CPB, Group 1 (n = 25) served as the control and in, Group 2 (n= 25), an N-MUF of 3000 ml was performed, using a BC140plus filter after weaning from CPB. Blood samples were taken after the induction of anesthesia, before CPB, before CPB weaning, 30 minutes after CPB and at 6, 24 and 48 hours postoperatively. Primary outcomes were plasma levels of lipopolysaccharide-binding protein (LBP), terminal complement complex (C5b9) and cytokines (IL-6, IL-10, IL-1beta, TNF-α). Secondary outcomes focused on differences in the clinical outcome. A significant reduction in LBP concentration (preoperatively: 23.8±8.4 pg/ml, postoperatively: 14.2±12.9 pg/ml) and C5b9 (preoperatively: 4.18±2.6 pg/ml, postoperatively: 3.05±2.39 pg/ml) were detected 6 hours after N-MUF. In the N-MUF group, significantly lower concentrations of lactate could be detected in the early postoperative period. Furthermore, postoperative chest tube blood loss was significantly lower in the N-MUF group at 24 and 48 hours. N-MUF leads to a significant reduction of lipopolysaccharide-binding protein and terminal complement complex and was associated with reduced blood loss and postoperative lactate concentrations shortly after surgery.

Topical Application of Tranexamic Acid to Reduce Post-Operative Bleeding in Coronary Artery Bypass Surgery

Abstract 3432Patients who undergo on-pump coronary artery bypass graft surgery (CABG) are at an increased risk of bleeding due physiologic, mechanical and pharmacologic disruption of hemostasis. The use of topically applied antifibrinolytic agents has been explored as a blood-conservation adjunct to reduce post-operative bleeding in cardiac surgery. Analysis of pooled results in a meta-analysis published by Abrishami et al. in 2009 showed that a significant reduction in blood loss could be achieved utilizing topical tranexamic acid in the absence of concurrent intravenous antifibrinolytic agents. However, current blood conservation clinical practice guidelines recommend the use of intravenous lysine analogues to limit peri-operative blood loss.Presently, there is no published prospective data evaluating blood loss in CABG patients who have received intravenous tranexamic acid, plus topical tranexamic acid versus placebo. Our study was designed to determine whether combined intravenous and topical application of tranexamic acid would reduce post-CABG blood loss in low-risk bypass surgery candidates. A sample calculation based on pilot study data analysis concluded that a minimum total of 74 patients was required, allowing 80% power to detect a 200mL difference in total blood loss (Type I error = 0.05) between groups.In our prospective, double-blind, randomized controlled trial, patients enrolled were randomly assigned to receive an intra-operative cardiac bath of either normal saline or tranexamic acid solution prior to sternotomy closure. All participants received intravenous tranexamic acid prior to the initiation of circulatory bypass. Research subject participation ended upon transfer out of the intensive care unit. Primary outcomes included the total volume of chest tube blood loss and number of transfusions administered following CABG. Secondary outcomes included chest tube loss volumes at 6 hours and 12 hours.Between December 1, 2011 and April 30, 2012, a total of 41 patients who underwent randomization were included in final data analysis. Baseline characteristics of patients enrolled in both groups were similar. Post-CABG losses at chest tube removal were found to be significantly reduced in the patients who received topical tranexamic acid. Mean chest tube loss in the placebo group (n=18) was 789mL versus 632mL in the topical tranexamic acid group (n=23), with a difference of 157mL (Figure 1, p value of student t-test 0.0493). A significantly greater proportion of patients in the placebo group were found to bleed more than 700mL at chest tube removal, in comparison with the topical tranexamic acid group (72.2% versus 30.4%, p value of chi-squared test 0.0079). Chest tubes remained in situ for a mean duration of 20 hours and 19 hours, respectively. None of the patients received post-operative red cell transfusions. One patient, randomized to the topical tranexamic acid group, received a single dose each of platelets and cryoprecipitate post-operatively. The application of topical tranexamic acid did not significantly reduce blood loss at 6 hours and 12 hours, with a difference of 76mL (p=0.1876) and 106mL (p=0.0930) respectively.The application of topical tranexamic acid reduces post-operative blood loss in patients undergoing on-pump CABG who have received intravenous tranexamic acid. There was no difference in blood product use between groups. Further studies must be carried out to investigate long-term outcomes of this practice and its applicability in high-risk cardiac surgery patients. (ClinicalTrials.gov number, NCT01519245.) [Display omitted] Disclosures:Off Label Use: Intravenous and topical application of tranexamic acid in cardiac surgery.

Influence of PAI-1 Gene Promoter-675 (4G/5G) Polymorphism on Fibrinolytic Activity After Cardiac Surgery Employing Cardiopulmonary Bypass

The plasminogen activator inhibitor type-1 (PAI-1) gene promoter contains 675 (4G/5G) polymorphism. The aim of this study was evaluate the effect of the PAI-1 promoter-675 (4G/5G) polymorphism on the concentrations of PAI-1 and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex and bleeding volume after on-pump cardiac surgery. A total of 90 patients were included in the study at Pauls Stradins Clinical University Hospital. Seven patients were excluded due to surgical bleeding. Eighty-three patients were classified according to the PAI-1 genotype: 21 patients had the 4G/4G genotype; 42, the 4G/5G genotype; and 20, the 5G/5G genotype. The following fibrinolysis parameters were recorded: the PAI-1 level preoperatively, D-dimer level at 0, 6, and 24 hours after surgery, and t-PA/PAI-1 complex level 24 hours postoperatively. A postoperative bleeding volume was registered in mL 24 hours after surgery. The patients with the 5G/5G genotype had significantly lower preoperative PAI-1 levels (17 [SD, 10.8] vs. 24 ng/mL [SD, 9.6], P=0.04), higher D-dimer levels at 6 hours (371 [SD, 226] vs. 232 ng/mL [SD, 185], P=0.03) and 24 hours (326 [SD, 207] vs. 209 ng/mL [SD, 160], P=0.04), and greater postoperative blood loss (568 [SD, 192] vs. 432 mL [168], P=0.02) compared with the 4G/4G carriers. There were no significant differences in the levels of the t-PA/PAI-1 complex comparing different genotype groups. The carriers of the 5G/5G genotype showed the lower preoperative PAI-1 levels, greater chest tube blood loss, and higher D-dimer levels indicating that the 5G/5G carriers may have enhanced fibrinolysis.

Use of prothrombin complex concentrate for excessive bleeding after cardiac surgery

Prothrombin complex concentrates (PCCs) are sometimes used as 'off label' for excessive bleeding after cardiopulmonary bypass (CPB). The main objective of this study was to retrospectively evaluate the clinical and biological efficacy of PCC in this setting. We reviewed the charts of all patients who had undergone cardiac surgery under CPB in our institution for 2 years. Patients treated for active bleeding with haemostatic therapy were identified. Chest tube blood loss was quantified postoperatively in the first 24 h. Coagulation parameters were recorded at intensive care unit admission and in the patient's first 24 h. Thromboembolic complications were also ascertained. Seventy-seven patients out of the 677 studied (11.4%) were included: PCC was solely administered in 24 patients (group I), fresh frozen plasma in 26 (group II) and both in 27 (group III). The mean dose of PCC was 10.0 UI/kg ± 3.5 for group I vs 14.1 UI/kg ± 11.2 for group III (P = 0.09). Initial blood loss in the first hour was different between the three groups (P = 0.05): 224 ± 131 ml for group I, 369 ± 296 ml for group II and 434 ± 398 ml for group III. Only group I vs group III presented a significant difference (P = 0.02). Variations of blood loss over time were no different according to the treatment groups (P = 0.12). Reductions in blood loss expressed in percentage showed no difference between the three groups after 2 h: 54.5% (68.6-30.8) for group I; 45.0% (81.6-22.2) for group II; 57.6 (76.0-2.1) for group III; (P = 0.89). Re-exploration for bleeding involved 1 patient in group I (4%), 2 in group II (8%) and 10 in group III (37%) (P = 0.002). Except for fibrinogen, variations of prothrombin time, activated partial thromboplastin time and platelets with time were not different according to the treatment groups. Cerebral infarction occurred in one patient in group II. Administration of low-dose of PCC significantly decreased postoperative bleeding after CPB.

Mortality Benefit With Prasugrel in the TRITON–TIMI 38 Coronary Artery Bypass Grafting Cohort: Risk-Adjusted Retrospective Data Analysis

The objective of this study was to characterize the bleeding, transfusion, and other outcomes of patients related to the timing of prasugrel or clopidogrel withdrawal before coronary artery bypass grafting (CABG). There is little evidence to guide clinical decision making regarding the use of prasugrel in patients who may need urgent or emergency CABG. Experience with performing CABG in the presence of clopidogrel has raised concern about perioperative bleeding complications that are unresolved. A subset of the TRITON-TIMI 38 study (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38), in which patients with acute coronary syndrome were randomized to treatment with aspirin and either clopidogrel or prasugrel, underwent isolated CABG (N = 346). A supplemental case report form was designed and administered, and the data combined with the existing TRITON-TIMI 38 database. Baseline imbalances were corrected for using elements of the European System for Cardiac Operative Risk Evaluation and The Society of Thoracic Surgeons predictive algorithm. A significantly higher mean 12-h chest tube blood loss (655 ± 580 ml vs. 503 ± 378 ml; p = 0.050) was observed with prasugrel compared with clopidogrel, without significant differences in red blood cell transfusion (2.1 U vs. 1.7 U; p = 0.442) or the total donor exposure (4.4 U vs. 3.0 U; p = 0.463). All-cause mortality was significantly reduced with prasugrel (2.31%) compared with 8.67% with clopidogrel (adjusted odds ratio: 0.26; p = 0.025). Despite an increase in observed bleeding, platelet transfusion, and surgical re-exploration for bleeding, prasugrel was associated with a lower rate of death after CABG compared with clopidogrel.

Normovolemic modified ultrafiltration is associated with better preserved platelet function and less postoperative blood loss in patients undergoing complex cardiac surgery: A randomized and controlled study

The purpose of the investigation was to study the impact of normovolemic modified ultrafiltration (N-MUF) on hemostasis and perioperative blood loss. Fifty patients scheduled for elective complex cardiac surgery were enrolled in this prospective, randomized, and controlled study. Patients were randomized into a control group (n = 25) or an N-MUF group (n = 25). N-MUF was performed using a BC140plus Filter (Maquet Cardiopulmonary AG, Hirrlingen, Germany) in the N-MUF group. Blood samples were taken before (T1) and 30 minutes after (T2) N-MUF in the N-MUF group and at corresponding time points in the control group. Platelet function analyses (TRAPtest, ASPItest, ADPtest) using multiple electrode aggregometry (Multiplate, Dynabyte, Munich, Germany), thrombelastometry (ROTEM, Pentapharm GmbH, Munich, Germany), and conventional laboratory coagulation analyses were performed at each time point. Intraoperative and postoperative transfusion requirements, hemostatic therapy, and blood loss were recorded. There were no significant group differences in demographic or surgical data. At T1, platelet aggregation revealed no significant group differences in the TRAPtest, ASPItest, or ADPtest. Platelet aggregation at T2 was significantly higher in the N-MUF group compared with the control group in the TRAPtest (65 [50/87] U vs 44 [28/51]; P < .001), the ASPItest (52 [36/69] U vs 22 [8/47] U; P = .001), or the ADPtest (39 [28/51] U vs 28 [19/39] U; P = .009). The postoperative chest tube blood loss was significantly lower in the N-MUF at 24 hours (890 [500/1100] mL vs 1075 [800/1413] mL in the N-MUF group vs the control group; P = .039) and 48 hours (900 [550/1350] mL vs 1400 [900/1750] mL; P = .026) postoperatively. Conventional laboratory coagulation analyses and thrombelastometric parameters did not differ within the groups at T1 or T2. N-MUF improved general platelet aggregation and reduced postoperative blood loss in a significant manner. However, performing N-MUF did not result in less postoperative transfusion requirements.

Transfusion Requirements and Outcomes In the Cohort of Patients Undergoing Isolated CABG Treated with Prasugrel or Clopidogrel: TRITON-TIMI 38 Data Analysis.

AbstractAbstract 1108▪Coronary artery bypass grafting (CABG)-related bleeding and associated transfusion support are concerns with dual antiplatelet therapy. The amount and the type of blood products transfused may be influenced by patient characteristics, procedural characteristics, acquired hemostatic defects, regional standard of care, and the amount of perioperative blood loss. Withdrawal of clopidogrel 5 days prior or prasugrel 7 days prior to CABG is suggested by the respective product labels to reduce the potential for CABG-related bleeding. Accordingly, a cohort of 422 patients undergoing isolated CABG in TRITON-TIMI 38 (PRASugrel n=208; CLOPidogrel n=214) was analyzed retrospectively to characterize the risk adjusted (using predicted risk of transfusion - Magovern, et al. Ann Thorac Surg 1996;61:27-32) difference in transfusion requirements between prasugrel and clopidogrel. Seventy-six patients who never received study drug or who received open label thienopyridine treatment prior to CABG were excluded. Packed red blood cells (PRBC) were the most frequently used blood product while platelet transfusions were relatively infrequent and regionally specific. No difference was noted in mean predicted transfusion risk score (TRS) between cohorts (PRAS 2.13 vs. CLOP 2.31; p=0.53; two-sided p value per ANOVA). TRS was associated with the number of units of PRBC transfused (p < 0.0001). Overall, there were significantly higher mean 12 hour chest tube loss (655 ±580 ml vs. 503± 378 ml; Kruskal-Wallis p=0.050) and platelet transfusion rates (18% vs. 9.8%; Pearson's chi-square p=.033) with PRAS. However, there were no statistically significant differences in PRBC transfusion units (mean 2.1±3.0 PRAS vs. 1.7±2.2 CLOP; Kruskal-Wallis p=0.44) or total donor exposure units (PRBC + whole blood + platelets + cryoprecipitate + fresh frozen plasma) (4.4±7.6 PRAS vs. 3.0±4.5 CLOP; Kruskal-Wallis p=0.46), although all of the analyses presented are underpowered. Total donor exposures were correlated with chest tube blood loss at 12 hours and the correlations were similar for both cohorts (PRAS, r=0.42; CLOP, r=0.45) (Figure). Transfusion requirements and blood loss by days from last dose categories are presented in the Table. Fifty-four (54)%, 22%, and 24% of patients went to CABG surgery ≤5 days, 6–7 days, and >7 days from the last dose of study drug, respectively (days from last dose to CABG unknown for 0.6% of patients). A significantly higher number of platelet units were used postoperatively in the PRAS patients going to surgery ≤5 days after withdrawal of drug. There is no suggestion of excess blood loss or excess of total units of blood transfusions after 7 days for PRAS or CLOP. In an analysis adjusted for the predicted risk of mortality (using Society of Thoracic Surgeons mortality score), total donor exposures were not associated with increased mortality risk [all-cause death within 30 days following CABG (odds ratio, 1.05 (0.97- 1.13) p=0.25; logistic regression analysis]. In addition, PRAS was independently associated with a reduction in mortality (PRAS, 1.2%; CLOP, 6.9%; p=0.027). In summary, the amount of blood products transfused is significantly influenced by patient and surgical characteristics, as well as by agents that can inhibit the hemostatic system. However, despite increased blood loss and use of greater numbers of platelets in a higher percentage of patients within the PRAS cohort, use of PRAS was associated with improved outcomes in the isolated CABG cohort of TRITON-TIMI 38. [Display omitted] Disclosures:Goodnough:Eli Lilly and Company: Consultancy. Despotis:Eli Lilly Company: Consultancy. Levy:Eli Lilly Company: Consultancy, Research Funding. Short:Eli Lilly & Company: Employment, Equity Ownership. Weerakkody:Eli Lilly & Company: Employment, Equity Ownership. Lenarz:Eli Lilly & Company: Employment, Equity Ownership.

A Phase III Randomized Trial of Lobectomy Versus Limited Resection for Small-sized Peripheral Non-small Cell Lung Cancer (JCOG0802/WJOG4607L)

A Phase III study was started in Japan to evaluate the non-inferiority in overall survival of segmentectomy compared with lobectomy in patients with small-sized (diameter </=2 cm) peripheral non-small cell lung cancer, excluding radiologically determined non-invasive cancer. This study began in August 2009, and a total of 1100 patients will be accrued from 71 institutions within 3 years. The primary endpoint is overall survival. The secondary endpoints are post-operative respiratory function, relapse-free survival, proportion of local recurrence, adverse events, proportion of patients who complete segmentectomy, duration of hospitalization, duration of chest tube placement, operation time, blood loss and number of auto-sutures used. This study is one of the first intergroup studies in Japan between the Japan Clinical Oncology Group and the West Japan Oncology Group.

Defining the role of recombinant activated factor VII in pediatric cardiac surgery: Where should we go from here?*

Postoperative hemorrhage is a recognized complication of pediatric cardiac surgery. Both the immature coagulation system and increased susceptibility to hemodilution increase the likelihood of pediatric patients developing coagulopathy when compared with adult counterparts. Treatment options remain limited. Recombinant factor VII (rFVIIa) is a hemostatic agent increasingly used to reduce hemorrhage in other surgical settings, the role of which is unclear in this population. This article systematically reviews the published literature on the use of rFVIIa in pediatric cardiac surgery. A systematic literature search identified reports of rFVIIa administration in pediatric patients undergoing cardiac surgery. Where possible, individual patient-specific data were extracted and pooled statistical analysis was performed. Twenty-nine articles reporting on the administration of rFVIIa to 169 patients were identified. rFVIIa has been administered to patients with predefined congenital abnormalities of hemostasis to arrest hemorrhage refractory to other interventions and prophylactically in the hope of reducing blood loss. Treatment regimens vary widely, in terms of both first and cumulative dose. Data on chest tube blood loss and two markers of coagulation were pooled and analyzed, and significant improvements were demonstrated. Mortality was 4.4% for the entire cohort but 20% of patients on extracorporeal membrane oxygenation suffered significant thromboembolic complications. rFVIIa has an increasingly accepted role in the management of patients with congenital coagulopathies undergoing major surgery. However, randomized trials are required to define the role of rFVIIa as an adjunct to control major hemorrhage in the pediatric cardiac surgical population. Any future work must focus not only on benefits but also on patient safety, particularly, risk of morbid thromboembolic complication.

Topical application of antifibrinolytic drugs for on-pump cardiac surgery: a systematic review and meta-analysis

This systematic review aimed to evaluate the efficacy and safety of topical application of antifibrinolytic drugs to reduce postoperative bleeding and transfusion requirements in patients undergoing on-pump cardiac surgery. We searched The Cochrane Library, MEDLINE, EMBASE and SCI-EXPANDED for all randomized controlled trials on the topic. Trial inclusion, quality assessment, and data extraction were performed independently by two authors. Standard meta-analytic techniques were applied. Eight trials (n = 622 patients) met our inclusion criteria. The medication/placebo was applied into the pericardial cavity and/or mediastinum at the end of cardiac surgery. Seven trials compared antifibrinolytic agents (aprotinin or tranexamic acid) versus placebo. They showed that, on average, topical use of antifibrinolytic agents reduced the amount of 24-h postoperative chest tube (blood) loss by 220 ml (95% confidence interval: -318 to -126, P < 0.00001, I (2) = 93%) and resulted in a saving of 1 unit of allogeneic red blood cells per patient (95% confidence interval: -1.54 to -0.53, P < 0.0001, I (2) = 55%). The incidence of blood transfusion was not significantly changed following topical application of the medications. One study comparing topical versus intravenous administration of aprotinin found comparable results between the two methods of administration for the above-mentioned outcomes. No adverse effects were reported following topical use of the medications. This review suggests that topical application of antifibrinolytics can reduce postoperative bleeding and transfusion requirements in patients undergoing on-pump cardiac surgery. These promising findings need to be confirmed by more trials with large sample size using patient-related outcomes and more assessments regarding the systemic absorption of the medications.

Postoperative Bleeding in Cardiac Surgery

Plasminogen activator inhibitor 1 (PAI-1) attenuates the conversion of plasminogen to plasmin. Polymorphisms of the PAI-1 gene are associated with varying PAI-1 levels and risk of prothrombotic events in nonsurgical patients. The purpose of this study, a secondary analysis of a clinical trial, was to investigate whether PAI-1 genotype affects the efficacy of tranexamic acid (TA) in reducing postoperative chest tube blood loss of patients undergoing cardiopulmonary bypass. Fifty patients were classified according to PAI-1 genotype (4G/4G, 4G/5G, or 5G/5G). Twenty-four received 2 g TA before and after cardiopulmonary bypass, whereas 26 received placebo. The authors recorded data related to coagulation, fibrinolysis, and bleeding before surgery, at admission to the intensive care unit (0 h), and 4 and 24 h later. In patients not receiving TA, those with the 5G/5G genotype had significantly higher chest tube blood loss and transfusion requirements compared with patients with the other genotypes at all time points. Patients with the 5G/5G genotype receiving TA showed significantly lower blood loss compared with the placebo group. There were no significant differences in blood loss or transfusion requirements between patients with the 4G/4G genotype when TA was used. Plasminogen activator inhibitor-1 5G/5G homozygotes who did not receive TA showed significantly greater postoperative bleeding than patients with other PAI-1 genotypes. 5G/5G homozygotes who received TA showed the greatest blood-sparing benefit.

This Month in Anesthesiology

749The goal of in-flight medical assistance is to stabilize the patient and advise the crew as to a diagnosis and treatment.659Breathing hydrogen sulfide induces a “suspended animation-like” state.627Consequences of opioid-induced sleep inhibition are important concerns in postoperative patients.596Iribarren et al . used data obtained from a randomized, double-blind, placebo-controlled study to explore the possible links between genotype and efficacy of tranexamic acid (TA) administered before and after cardiopulmonary bypass surgery. The original 50 study patients (the study had been halted due to a higher rate of excessive bleeding in the placebo group) had been classified according to plasminogen activator inhibitor-1 (PAI-1) genotype. The authors' secondary analysis from this trial revealed that in patients not receiving TA, those with the 5G/5G genotype had significantly higher chest tube blood loss and transfusion requirements compared with other patients. 5G/5G homozygotes who received TA showed the greatest blood-sparing benefit.703Ilfeld et al. compared a 4-day ambulatory continuous femoral nerve block (cFNB) to overnight cFNB in patients who had undergone tricompartment total knee arthroplasty. Compared with those receiving overnight cFNB, patients in the group receiving four days of perineural ropivacaine (via a portable infusion pump) showed a 53% decrease in the time required to reach three important discharge criteria: adequate analgesia, independence from intravenous analgesics, and ambulation of at least 30 m.634Statins appear to confer greater cardiovascular benefits in diabetic patients. To further elucidate this observed benefit, Gu et al . designed experiments to investigate whether simvastatin improves the beneficial effects of ischemic preconditioning during hyperglycemia in dogs subjected to coronary artery occlusion and reperfusion. Simvastatin restored the cardioprotective effects of ischemic preconditioning during hyperglycemia via nitric oxide–mediated signaling. The results suggest that enhanced cardioprotective signaling could be a mechanism for statin-induced decreases in perioperative cardiovascular risk.568In this issue, McGregor et al . report on their post hoc analysis of data from the large multicenter Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST). In the IHAST, anesthesia was dictated by a limited-options protocol and the decision about using nitrous oxide was left to individual anesthesiologists. Of the 1,000 patients for whom data were available, 373 had received nitrous oxide. According to various instruments used in the IHAST to assess neurologic and neuropsychological outcomes, intraoperative use of nitrous oxide was not associated with delayed ischemic neurologic deficits, long-term neurologic deficits, or neuropsychological deficits. See the accompanying Editorial View on page 553 559This article has been selected for the Anesthesiology CME Program. See the accompanying Editorial View on page 551 .

Excessive Bleeding and Transfusion in a Prior Cardiac Surgery is Associated with Excessive Bleeding and Transfusion in the Next Surgery

If there is a genetic predisposition to excessive bleeding, there should be an association in excessive blood loss between multiple cardiac surgeries. We retrospectively determined in 174 patients the association of excessive bleeding between 2 cardiac surgeries with cardiopulmonary bypass between January 19, 1990 and June 25, 2002. Excessive bleeding was defined by 2 criteria: (a) postoperating room chest tube blood loss over 24 h more than or equal to 750 mL (chest tube drainage [CTD] > or = 750) and (b) transfusion of any non-red blood cell (RBC) blood products. Logistic regression was used to estimate the association between excessive bleeding at the first and second cardiac procedures. The logistic regression models for CTD > or = 750 in the second surgery determined that CTD > or = 750 in the first surgery compared to CTD < 750 had an unadjusted odds ratio of 2.18 (P = 0.03) and an odds ratio of 2.42 (P = 0.03) when adjusted for age, sex, body surface area, preoperative anticoagulant use, cardiopulmonary bypass duration, and procedure type at second surgery. The logistic regression model for any non-RBC use in the second surgery determined that any non-RBC use in the first surgery compared with no non-RBC use had an unadjusted odds ratio of 2.32 (P = 0.02) and an odds ratio of 2.55 (P = 0.02) when adjusted for age, sex, body surface area, preoperative anticoagulant use, cardiopulmonary bypass duration, and procedure type at second surgery. We conclude that a history of excessive bleeding during the first operation is associated with more than two times increased risk for excessive bleeding in the second surgery.